Aiuti, A.; Slavin, S.; Aker, M.; Ficara, F.; Deola, S.; Mortellaro, A.; Morecki, S.; Andolfi, G.;
Tabucchi, A.; Carlucci, F.; Marinello, E.; Cattaneo, F.; Vai, S.; Servida, P.; Miniero, R.;
Roncarolo, M. G.; Bordignon, C. (2002). Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science 296: 2410-2413.
Alliot, F.; Godin, I.; Pessac, B. (1999). Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res 117: 145-152.
Austyn, J. M.; Gordon, S. (1981). F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol 11: 805-815.
Bagley, J.; Aboody-Guterman, K.; Breakefield, X.; Iacomini, J. (1998). Long-term expression of the gene encoding green fluorescent protein in murine hematopoietic cells using retroviral gene transfer. Transplantation 65: 1233-1240.
Banati, R. B.; Hoppe, D.; Gottmann, K.; Kreutzberg, G. W.; Kettenmann, H. (1991).
A subpopulation of bone marrow-derived macrophage-like cells shares a unique ion channel pattern with microglia. J Neurosci Res 30: 593-600.
Banati, R. B.; Gehrmann, J.; Schubert, P.; Kreutzberg, G. W. (1993). Cytotoxicity of microglia.
Glia 7: 111-118.
Banati, R. B.; Graeber, M. B. (1994). Surveillance, intervention and cytotoxicity: is there a protective role of microglia? Dev Neurosci 16: 114-127.
Bechmann, I.; Priller, J.; Kovac A.; Böntert, M.; Wehner, T.; Klett, F. F.; Bohsung, J.; Stuschke, M.; Dirnagl, U.; Nitsch, R. (2001). Immune surveillance of mouse brain perivascular spaces by blood-borne macrophages. Eur J Neurosci 14: 1651-1658.
Bierhuizen, M. F.; Westerman, Y.; Visser, T. P.; Dimjati, W.; Wognum, A. W.; Wagemaker, G.
(1997). Enhanced green fluorescent protein as selectable marker of retroviral-mediated gene transfer in immature hematopoietic bone marrow cells. Blood 90: 3304-3315.
Brand, A. (1995). GFP in Drosophila. Trends Genet 11: 324-325.
Brazelton, T. R.; Rossi, F. M.; Keshet, G. I.; Blau, H. M. (2000). From marrow to brain:
expression of neuronal phenotypes in adult mice. Science 290: 1775-1779.
Chalfie, M.; Tu, Y.; Euskirchen, G.; Ward, W. W.; Prasher, D. C. (1994). Green fluorescent protein as a marker for gene expression. Science 263: 802-805.
Chiang, C. S.; McBride, W. H.; Withers, H. R. (1993). Radiation-induced astrocytic and microglial responses in mouse brain. Radiother Oncol 29: 60-68.
Cicciarello, R.; d'Avella, D.; Gagliardi, M. E.; Albiero, F.; Vega, J.; Angileri, F. F.;
D'Aquino, A.; Tomasello, F. (1996). Time-related ultrastructural changes in an experimental model of whole brain irradiation. Neurosurgery 38: 772-779.
Cody, C. W.; Prasher, D. C.; Westler, W. M.; Prendergast, F. G.; Ward, W. W. (1993). Chemical structure of the hexapeptide chromophore of the Aequorea green-fluorescent protein.
Biochemistry 32: 1212-1218.
Cormack, B. P.; Valdivia, R. H.; Falkow, S. (1996). FACS-optimized mutants of the green fluorescent protein (GFP). Gene 173: 33-38.
de Bruijn, M. F.; Slieker, W. A.; van der Loo, J. C.; Voerman, J. S.; van Ewijk, W.; Leenen, P. J.
de Groot, C. J.; Huppes, W.; Sminia, T.; Kraal, G.; Dijkstra, C. D. (1992). Determination of the origin and nature of brain macrophages and microglial cells in mouse central nervous system, using non-radioactive in situ hybridization and immunoperoxidase techniques.
Glia 6: 301-309.
del Zoppo, G. J.; Becker, K. J.; Hallenbeck, J. M. (2001). Inflammation after stroke: is it harmful? Arch Neurol 58: 669-672.
Dirnagl, U.; Iadecola, C.; Moskowitz, M. A. (1999). Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22: 391-397.
Eglitis, M. A.; Mezey, E. (1997). Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci U S A 94: 4080-4085.
Feuerstein, G.; Wang, X. (2001). Inflammation and Stroke - Benefits without harm? Arch Neurol 58: 672-674.
Flaris, N. A.; Densmore, T. L.; Molleston, M. C.; Hickey, W. F. (1993). Characterization of microglia and macrophages in the central nervous system of rats: definition of the differential expression of molecules using standard and novel monoclonal antibodies in normal CNS and in four models of parenchymal reaction. Glia 7: 34-40.
Flügel, A.; Hager, G.; Horvat, A.; Spitzer, C.; Singer, G. M.; Graeber, M. B.; Kreutzberg, G. W.;
Schwaiger, F. W. (2001). Neuronal MCP-1 expression in response to remote nerve injury.
J Cereb Blood Flow Metab 21: 69-76.
Glass, J. D.; Wesselingh, S. L. (2001). Microglia in HIV-associated neurological diseases.
Microsc Res Tech 54: 95-105.
Goldman, S.; Roy, N. (2000). Reply to “Human neural progenitor cells: better blue than green?”
Nat Med 6: 483-484.
Hacein-Bey-Abina, S.; Le Deist, F.; Carlier, F.; Bouneaud, C.; Hue, C.; de Villartay, J. P.;
Thrasher, A. J.; Wulffraat, N.; Sorensen, R.; Dupuis-Girod, S.; Fischer, A.; Cavazzana-Calvo, M. (2002). Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. NEJM 346: 1185-1193.
Hailer, N. P.; Heppner, F. L.; Haas, D.; Nitsch, R. (1998). Astrocytic factors deactivate antigen presenting cells that invade the central nervous system. Brain Pathol 8: 459-474.
Hara, H.; Huang, P. L.; Panahian, N.; Fishman, M. C.; Moskowitz, M. A. (1996). Reduced brain edema and infarction volume in mice lacking the neuronal isoform of nitric oxide synthase after transient MCA occlusion. J Cereb Blood Flow Metab 16: 605-611.
Hess, D. C.; Hill, W. D.; Martin-Studdard, A.; Carroll, J.; Brailer, J.; Carothers, J. (2002). Bone marrow as a source of endothelial cells and NeuN-expressing cells after stroke. Stroke 33:
1362-1368.
Hickey, W. F.; Kimura, H. (1987). Graft-vs-host disease elicits expression of class I and class II histocompatibility antigens and the presence of scattered T lymphocytes in rat central nervous system. Proc Natl Acad Sci U S A 84: 2082-2086.
Hickey, W. F.; Kimura, H. (1988). Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 239: 290-292.
Hickey, W. F.; Hsu, B. L.; Kimura, H. (1991). T-lymphocyte entry into the central nervous system. J Neurosci Res 28: 254-260.
Hickey, W. F. (1999). Leukocyte traffic in the central nervous system: the participants and their roles. Semin Immunol 11: 125-137.
Huang, W. Y.; Aramburu, J.; Douglas, P. S.; Izumo, S. (2000). Transgenic expression of green fluorescence protein can cause dilated cardiomyopathy. Nat Med 6: 482-43.
Iadecola, C. (1997). Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci 20: 132-139.
Imai, Y.; Ibata, I.; Ito, D.; Ohsawa, K.; Kohsaka, S. (1996). A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem Biophys Res Commun 224: 855-862.
Ito, D.; Imai, Y.; Ohsawa, K.; Nakajima, K.; Fukuuchi, Y.; Kohsaka, S. (1998). Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res Mol Brain Res 57: 1-9.
Kato, H.; Walz, W. (2000). The initiation of the microglial response. Brain Pathol 10: 137-143.
Kaur, C.; Hao, A. J.; Wu, C. H.; Ling, E. A. (2001). Origin of microglia. Microsc Res Tech 54:
2-9.
Kennedy, D. W.; Abkowitz, J. L. (1998). Mature monocytic cells enter tissues and engraft. Proc Natl Acad Sci U S A 95: 14944-14949.
Krall, W. J.; Challita, P. M.; Perlmutter, L. S.; Skelton, D. C.; Kohn, D. B. (1994). Cells expressing human glucocerebrosidase from a retroviral vector repopulate macrophages and central nervous system microglia after murine bone marrow transplantation. Blood 83: 2737-2748.
Kreutzberg, G. W. (1996). Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19: 312-318.
Krivit, W.; Sung, J. H.; Shapiro, E. G.; Lockman, L. A. (1995). Microglia: the effector cell for reconstitution of the central nervous system following bone marrow transplantation for lysosomal and peroxisomal storage diseases. Cell Transplant 4: 385-392.
Krivit, W.; Shapiro; E. G.; Peters,; E. G.; Peters,; Peters, C.; Wagner, J. E.; Cornu, G.;
Kurtzberg, J.; Wenger, D. A.; Kolodny, E. H.; Vanier, M. T.; Loes, D. J.; Dusenberry, K.;
Lockman, L. A. (1998). Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. NEJM 338: 1119-1126.
Kume, A.; Xu, R.; Ueda, Y.; Urabe, M.; Ozawa, K. (2000). Long-term tracking of murine hematopoietic cells transduced with a bicistronic retrovirus containing CD24 and EGFP genes. Gene Ther 7: 1193-1199.
Lassmann, H.; Zimprich, F.; Vass, K.; Hickey, W. F. (1991). Microglial cells are a component of the perivascular glia limitans. J Neurosci Res 28: 236-243.
Lawson, L. J.; Perry, V. H.; Gordon, S. (1992). Turnover of resident microglia in the normal adult mouse brain. Neuroscience 48: 405-415.
Limon, A.; Briones, J.; Puig, T.; Carmona, M.; Fornas, O.; Cancelas, J. A.; Nadal, M.; Garcia, J.;
Rueda, F.; Barquinero, J. (1997). High-titer retroviral vectors containing the enhanced green fluorescent protein gene for efficient expression in hematopoietic cells. Blood 90:
3316-3321.
Ling, E. A.; Wong, W. C. (1993). The origin and nature of ramified and amoeboid microglia: a historical review and current concepts. Glia 7: 9-18.
Lipton, P. (1999). Ischemic cell death in brain neurons. Physiological Reviews 79: 1431-1568.
Liu, H. S.; Jan M. S.; Chou C. K.; Chen P. H.; Ke N. J. (1999). Is green fluorescent protein toxic to the living cells? Biochem Biophys Res Commun 260: 712-717.
Markowitz, D.; Goff, S.; Bank, A. (1988). A safe packaging line for gene transfer: separating viral genes on two different plasmids. J Virol 62: 1120-1124.
Matsumoto, Y.; Fujiwara, M. (1987). Absence of donor-type major histocompatibility complex class I antigen-bearing microglia in the rat central nervous system of radiation bone marrow chimeras. J Neuroimmunol 17: 71-82.
Matzner, U.; Harzer, K.; Learish, R. D.; Barranger, J. A.; Gieselmann, V. (2000). Long-term expression and transfer of arylsulfatase A into brain of arylsulfatase A-deficient mice transplanted with bone marrow expressing the arylsulfatase A cDNA from a retroviral vector. Gene Ther 7: 1250-1257.
Matzner, U.; Hartmann, D.; Lullmann-Rauch, R.; Coenen, R.; Rothert, F.; Mansson, J. E.;
Fredman, P.; D'Hooge, R.; De Deyn, P. P.; Gieselmann, V. (2002). Bone marrow stem cell-based gene transfer in a mouse model for metachromatic leukodystrophy: effects on visceral and nervous system disease manifestations. Gene Ther 9: 53-63.
Mezey, E.; Chandross, K. J.; Harta, G.; Maki, R. A.; McKercher, S. R. (2000). Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290: 1779-1782.
Miranda, S. R.; Erlich, S.; Visser, J. W.; Gatt, S.; Dagan, A.; Friedrich VL Jr; Schuchman,;
Schuchman, E. H. (1997). Bone marrow transplantation in acid sphingomyelinase-deficient mice: engraftment and cell migration into the brain as a function of radiation, age, and phenotype. Blood 90: 444-452.
Miranda, S. R.; Erlich, S.; Friedrich VL Jr; Gatt,; Gatt, S.; Schuchman, E. H. (2000).
Hematopoietic stem cell gene therapy leads to marked visceral organ improvements and a delayed onset of neurological abnormalities in the acid sphingomyelinase deficient mouse model of Niemann-Pick disease. Gene Ther 7: 1768-1776.
Nakano, K.; Migita, M.; Mochizuki, H.; Shimada, T. (2001). Differentiation of transplanted bone marrow cells in the adult mouse brain. Transplantation 71: 1735-1740.
Okabe, M.; Ikawa, M.; Kominami, K.; Nakanishi, T.; Nishimune, Y. (1997). 'Green mice' as a source of ubiquitous green cells. FEBS Lett 407: 313-319.
Ono, K.; Takii, T.; Onozaki, K.; Ikawa, M.; Okabe, M.; Sawada, M. (1999). Migration of exogenous immature hematopoietic cells into adult mouse brain parenchyma under GFP-expressing bone marrow chimera. Biochem Biophys Res Commun 262: 610-614.
Padovan, C. S.; Bise, K.; Hahn, J.; Sostak, P.; Holler, E.; Kolb, H. J.; Straube, A. (1999).
Angiitis of the central nervous system after allogeneic bone marrow transplantation?
Stroke 30: 1651-1656.
Padovan, C. S.; Gerbitz, A.; Sostak, P.; Holler, E.; Ferrara, J. L.; Bise, K.; Straube, A. (2001).
Cerebral involvement in graft-versus-host disease after murine bone marrow transplantation. Neurology 56: 1106-1108.
Persons, D. A.; Allay, J. A.; Allay, E. R.; Smeyne, R. J.; Ashmun, R. A.; Sorrentino, B. P.;
Nienhuis, A. W. (1997). Retroviral-mediated transfer of the green fluorescent protein gene into murine hematopoietic cells facilitates scoring and selection of transduced progenitors in vitro and identification of genetically modified cells in vivo. Blood 90:
1777-1786.
Persons, D. A.; Allay, J. A.; Riberdy, J. M.; Wersto, R. P.; Donahue, R. E.; Sorrentino, B. P.;
Nienhuis, A. W. (1998). Use of the green fluorescent protein as a marker to identify and track genetically modified hematopoietic cells. Nat Med 4: 1201-1205.
Peters, S. O.; Kittler, E. L.; Ramshaw, H. S.; Quesenberry, P. J. (1995). Murine marrow cells expanded in culture with IL-3, IL-6, IL-11, and SCF acquire an engraftment defect in normal hosts. Exp Hematol 23: 461-469.
Poenaru, L. (2001). From gene transfer to gene therapy in lysosomal storage diseases affecting the central nervous system. Ann Med 33: 28-36.
Popovich, P. G.; Hickey, W. F. (2001). Bone marrow chimeric rats reveal the unique distribution of resident and recruited macrophages in the contused rat spinal cord. J Neuropathol Exp Neurol 60: 676-685.
Prasher, D. C.; Eckenrode, V. K.; Ward, W. W.; Prendergast, F. G.; Cormier, M. J. (1992).
Primary structure of the Aequorea victoria green-fluorescent protein. Gene 111: 229-233.
Priller, J.; Flügel, A.; Wehner, T.; Böntert, M.; Haas, C. A.; Prinz, M.; Fernandez Klett, F.;
Prass, K.; Bechmann, I.; de Boer, B. A.; Frotscher, M.; Kreutzberg, G. W.; Persons, D.
A.; Dirnagl, U. (2001a). Targeting gene-modified hematopoietic cells to the central nervous system: Use of green fluorescent protein uncovers microglial engraftment.
Nat Med 7: 1356-1361.
Priller, J.; Persons, D. A.; Klett, F. F.; Kempermann, G.; Kreutzberg, G. W.; Dirnagl, U. (2001b).
Neogenesis of cerebellar Purkinje neurons from gene-marked bone marrow cells in vivo.
J Cell Biol 155: 733-738.
Raivich, G.; Bohatschek, M.; Kloss, C. U.; Werner, A.; Jones, L. L.; Kreutzberg, G. W. (1999).
Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function. Brain Res Brain Res Rev 30: 77-105.
Rio Hortega, P. del (1932). Microglia. In: Penfield, W. (Ed.). Cytology and Cellular Pathology of the Nervous System, Vol. II; Hoeber, New York, 481-534.
Schluter, D.; Meyer, T.; Strack, A.; Reiter, S.; Kretschmar, M.; Wiestler, O. D.; Hof, H.;
Deckert, M. (2001). Regulation of microglia by CD4+ and CD8+ T cells: selective analysis in CD45-congenic normal and Toxoplasma gondii-infected bone marrow chimeras. Brain Pathol 11: 44-55.
Schmidtmayer, J.; Jacobsen, C.; Miksch, G.; Sievers, J. (1994). Blood monocytes and spleen macrophages differentiate into microglia-like cells on monolayers of astrocytes:
membrane currents. Glia 12: 259-267.
Sievers, J.; Parwaresch, R.; Wottge, H. U. (1994). Blood monocytes and spleen macrophages differentiate into microglia-like cells on monolayers of astrocytes: morphology. Glia 12:
245-258.
Silverman, A. J.; Sutherland, A. K.; Wilhelm, M.; Silver, R. (2000). Mast cells migrate from blood to brain. J Neurosci 20: 401-408.
Spangrude, G. J. (1994). Assessment of Lymphocyte Development in Radiation Bone Marrow
Stoll, G.; Jander, S. (1999). The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 58: 233-247.
Streit, W. J.; Graeber, M. B.; Kreutzberg, G. W. (1989). Expression of Ia antigen on perivascular and microglial cells after sublethal and lethal motor neuron injury. Exp Neurol 105:
115-126.
Streit, W. J.; Graeber, M. B. (1993). Heterogeneity of microglial and perivascular cell populations: insights gained from the facial nucleus paradigm. Glia 7: 68-74.
Thomas, W. E. (1999). Brain macrophages: on the role of pericytes and perivascular cells. Brain Res Brain Res Rev 31: 42-57.
Tsien, R. Y. (1998). The green fluorescent protein. Annu Rev Biochem 67: 509-544.
Unger, E. R.; Sung, J. H.; Manivel, J. C.; Chenggis, M. L.; Blazar, B. R.; Krivit, W. (1993).
Male donor-derived cells in the brains of female sex-mismatched bone marrow transplant recipients: a Y-chromosome specific in situ hybridization study. J Neuropathol Exp Neurol 52: 460-470.
Wada, R.; Tifft, C. J.; Proia, R. L. (2000). Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation.
Proc Natl Acad Sci U S A 97: 10954-10959.
Walkley, S. U.; Thrall, M. A.; Dobrenis, K.; Huang, M.; March, P. A.; Siegel, D. A.;
Wurzelmann, S. (1994). Bone marrow transplantation corrects the enzyme defect in neurons of the central nervous system in a lysosomal storage disease. Proc Natl Acad Sci U S A 91: 2970-2974.
Wekerle, H.; Linnington, G.; Lassmann, H. M. R. (1986). Cellular immune reactivity within the CNS. Trends in Neurosciences 9: 271-277.
Wu, Y. P.; McMahon, E. J.; Matsuda, J.; Suzuki, K.; Matsushima, G. K.; Suzuki, K. (2001).
Expression of immune-related molecules is downregulated in twitcher mice following bone marrow transplantation. J Neuropathol Exp Neurol 60: 1062-1074.
Yenari, M. A.; Dumas, T. C.; Sapolsky, R. M.; Steinberg, G. K. (2001). Gene therapy for treatment of cerebral ischemia using defective herpes simplex viral vectors. Neurol Res 23: 543-552.
Abkürzungen
CD Differenzierungsantigen, engl. cluster determinant EDTA Ethylendiamintetraazetat
EGFP Verstärkte Variante des grünen fluoreszierenden Proteins, engl. enhanced green fluorescent protein
FACS Fluoreszenz gesteuerte Zellsortierung, engl. Fluorescence-activated cell sorting
FCS fötales Kälberserum, engl. fetal calf serum FITC Fluoresceinisothiocyanat
GFP grünes fluoreszierendes Protein
GZL Globoidzellen-Leukodystrophie, Krabbe-Krankheit
HIV Humanes Immunodefizienzvirus
Iba1 ionisiertes Calcium bindendes Adaptermolekül 1
ICAM-1 Interzelluläres Zelladhäsionsmolekül 1, engl. intercellular cell adhesion molecule 1
IL Interleukin
iNOS induzierbare Stickstoffmonoxidsynthetase
KHCO3 Kaliumhydrogencarbonat
KMT Knochenmarktransplantation
MCP Monozyten-Chemoanziehendes Protein, engl. monocyte chemoattractant protein
MHC Hauptgewebehistokompatibilitätskomplex, engl. major histocompatibility complex
NaCl Natriumchlorid, physiologische Kochsalzlösung
NH4Cl Ammoniumchlorid
NO Stickstoffmonoxid
NOS Stickstoffmonoxidsynthetase
PBS phosphatgepufferte natürliche Kochsalzlösung, engl. phosphate buffered saline
PE Phycoerythrin PFA Paraformaldehyd
rHuIL-6 rekombinantes humanes Interleukin 6
rMuIL-3 rekombinantes murines Interleukin 3
rSCF Stammzellfaktor aus der Ratte, engl. rat stem cell factor ZKM Zellkulturmedium
ZNS Zentralnervensystem
Danksagung
Im Laufe dieser Dissertation habe ich die Laborforschung mit all ihren Höhen und Tiefen kennengelernt. Zum Gelingen des Projektes haben viele Menschen beigetragen.
Herrn Prof. Dr. Ulrich Dirnagl danke ich für die Überlassung des Themas und die jederzeit und in jeder Hinsicht vorbildlich gewährte Unterstützung. Gleiches gilt für Herrn PD Dr. Josef Priller, der mich in der alltäglichen Arbeit betreute.
Während der experimentellen Phase habe ich eng mit meinem Freund und Mitdoktoranden Matthias Böntert zusammengearbeitet. In der unmittelbaren Arbeit habe ich vieles von meinem Mitdoktoranden Francisco Fernandez Klett gelernt. Dabei habe ich auch von Vorarbeiten meines Vorgängers, Herrn Matthias Heinze, profitiert. Allen dreien danke ich für die gute Zusammenarbeit in der „AG Grün“.
Herrn Dr. Konstantin Prass spreche ich meinen Dank und meine Anerkennung für die sorgfältig ausgeführten Ischämieoperationen aus.
Frau Dr. Dorette Freyer und Frau Renate Gusinda haben mir das ABC der Zellkultur vermittelt und bei kleinen und großen Problemen mit ihrer Erfahrung Hilfestellung leisten können, wofür ich beiden dankbar bin.
Herrn Dr. Bauke A. de Boer, zur Zeit der Experimente am Deutschen Rheumaforschungszentrum tätig, danke ich für die Einarbeitung in die Durchflusszytometrie, seinem Kollegen Dr. Thoralf Kaiser für die Unterstützung bei der Zellsortierung.
Herrn Dr. Werner Zuschratter vom Institut für Neurobiologie in Magdeburg bin ich dankbar für die dreidimensionale Rekonstruktion einer GFP-exprimierenden Mikrogliazelle.
Herrn PD Dr. Ingo Bechmann vom Institut für Anatomie der Charité spreche ich meinen Dank für produktive Diskussionen im Zusammenhang mit den Themenbereichen Quantifizierung und Immunhistochemie aus.
Der Charité danke ich für ein Forschungsstipendium, ohne welches ich mich diesem Projekt nicht so intensiv hätte widmen können.
Lebenslauf
Tim Wehner
18. Mai 1972 Geboren in Georgsmarienhütte, Landkreis Osnabrück Eltern: Doris Wehner, technische Zeichnerin
Klaus Wehner, Ingenieur
Schule
1978 – 1982 Grundschule Schledehausen
1982 – 1984 Orientierungsstufe Dom Osnabrück
1984 – 1991 Gymnasium Carolinum Osnabrück, Abitur am 31. Mai 1991
Zivildienst
Sept. 1991 – Okt. 1992 Krankenpflegehelfer, Marienhospital Osnabrück
Studium der Humanmedizin
Okt. 1992 – März 1994 Universität Kiel, unterbrochen durch eine schwere Erkrankung April 1994 – April 2001 Universität Witten/Herdecke
Aug. 1997 – Juni 1998 University of Aberdeen, Scotland;
Auslandsstipendium der Studienstiftung des deutschen Volkes Mai 1999 – April 2000 Experimenteller Teil der Dissertation in der Abteilung für
Experimentelle Neurologie der Charité, assoziiertes Mitglied im Graduiertenkolleg 238 „Schadensmechanismen im
Nervensystem“
Mai 2000 – März 2001 Praktisches Jahr
Innere Medizin MetroHealth Medical Center, Cleveland, Ohio, USA (Prof. G. Richard Olds, M. D.)
Neurologie Klinikum Wuppertal
(Prof. Dr. Johannes Jörg)
Chirurgie Evangelisches Krankenhaus Witten
Examina
April 1996 Ärztliche Vorprüfung
April 1997 1. Abschnitt der ärztlichen Prüfung April 1999 2. Abschnitt der ärztlichen Prüfung April 2001 3. Abschnitt der ärztlichen Prüfung
Juni 1997 USMLE Step 1
Juli 2001 USMLE Step 2 und „Clinical Skills Assessment“
Dezember 2001 USMLE Step 3
Auszeichnungen
1997-2001 Stipendiat der Studienstiftung des deutschen Volkes
Beruflicher Werdegang
Juli 2001 – Juni 2002 Arzt/Wissenschaftlicher Mitarbeiter in der Arbeitsgruppe
„Modellstudiengang“ an der Fakultät für Medizin der Universität Witten/Herdecke (Dr. Wilhelm E. Vermaasen)
Juni 2002 Beginn der Weiterbildung in Neurologie an der Case Western Reserve University / MetroHealth Medical Center (obligatorische “Internship” in Innerer Medizin) und an der Cleveland Clinic Foundation; Cleveland, Ohio, USA
Publikationsliste
Wehner, T.; Böntert, M.; Eyüpoglu, I.; Prass, K.; Klett, F. F.; Heinze, M.; Bechmann, I.;
Nitsch, R.; Kirchhoff, F.; Kettenmann, H.; Dirnagl, U.; Priller J. Bone marrow-derived cells expressing GFP under the control of the glial fibrillary acidic protein promoter do not differentiate into astrocytes in vitro and in vivo. Submitted.
Priller, J.; Flügel, A.; Wehner, T.; Böntert, M.; Haas, C. A.; Prinz, M.; Fernandez Klett, F.;
Prass, K.; Bechmann, I.; de Boer, B. A.; Frotscher, M.; Kreutzberg, G. W.; Persons, D. A.;
Dirnagl, U. (2001). Targeting gene-modified hematopoietic cells to the central nervous system: Use of green fluorescent protein uncovers microglial engraftment. Nat Med 7: 1356-1361.
Bechmann, I.; Priller, J.; Kovac, A.; Böntert, M.; Wehner, T.; Klett, F. F.; Bohsung, J.;
Stuschke, M.; Dirnagl, U.; Nitsch, R. (2001). Immune surveillance of mouse brain perivascular spaces by blood-borne macrophages. Eur J Neurosci 14: 1651-1658.
Kongressbeiträge
Wehner, T.; Böntert, M.; Eyüepoglu, I.; Fernandez, F.; Prass, K.; Bechmann, I.; Nitsch, R.;
Kirchhoff, F.; Dirnagl, U.; Priller, J. (November 2000). Bone marrow derived cells differentiate into microglia but not into GFAP-positive astroglia in vitro and in a transgenic mouse model. 30th Annual Meeting of the Society for Neuroscience, New Orleans (Poster).
Wehner, T.; Böntert, M.; Fernandez, F.; Heinze, M.; Prass, K.; Bohsung, J.; de Boer, B.;
Priller, J.; Dirnagl, U. (November 1999). Gfp as a tool to investigate the cns invasion of hematogenous cells under physiological and ischemic conditions. European Students Conference, Berlin (Vortrag und Poster).
Eidesstattliche Erklärung
Die vorliegende Dissertation habe ich selbst ohne unzulässige Hilfe Dritter verfasst. Die von mir benutzten Hilfsmittel und die Literatur habe ich vollständig angegeben. Diese Dissertation ist bislang nicht veröffentlicht, und sie wurde noch von keiner anderen Fakultät abgelehnt.
Berlin, den